Biology subjects

Jokerst, J. V.

Publications and source records attributed to Jokerst, J. V..

4 recordsLinked to original sources

bioRxiv2023

Activatable prodrug for controlled release of an antimicrobial peptide via the proteases overexpressed in Candida albicans and Porphyromonas gingivalis

We report the controlled release of an antimicrobial peptide using enzyme-activatable prodrugs to treat and detect Candida albicans and Porphyromonas gingivalis. Our motivation lies in the prevalence of these microorganisms in the subgingival area where the frequency of fungal colonization increases with periodontal disease. This work is based on an antimicrobial peptide that is both therapeutic and induces a color change in a nanoparticle reporter. This antimicrobial peptide was then built into a zwitterionic prodrug that quenches its activity until activation by a protease inherent to these pathogens of interest: SAP9 or RgpB for C. albicans and P. gingivalis, respectively. We first confirmed that the intact zwitterionic prodrug has negligible toxicity to fungal, bacterial, and mammalian cells absent a protease trigger. Next, the therapeutic impact was assessed via disk diffusion and viability assays and showed a minimum inhibitory concentration of 3.1 - 16 {micro}g/mL, which is comparable to the antimicrobial peptide alone (absent integration into prodrug). Finally, the zwitterionic design was exploited for colorimetric detection of C. albicans and P. gingivalis proteases. When the prodrugs were cleaved, the plasmonic nanoparticles aggregated causing a color change with a limit of detection of 10 nM with gold nanoparticles and 3 nM with silver nanoparticles. This approach has value as a convenient and selective protease sensing and protease-induced treatment mechanism based on bioinspired antimicrobial peptides. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/568833v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1e9cf5corg.highwire.dtl.DTLVardef@12cb36forg.highwire.dtl.DTLVardef@1b862f7org.highwire.dtl.DTLVardef@697946_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2022

Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains

To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-viral antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.

immunology↗

bioRxiv2022

Characterization of a miniaturized ultrasound transducer customized for oral health applications

ObjectiveTo customize a miniaturized ultrasound transducer to access full-mouth B-mode, color Doppler and spectral Doppler imaging for monitoring oral health. MethodsA customized periodontal ultrasound transducer SS-19-128 (19 MHz, 128 channels) with 1.8 cm wide and 1 cm thick was developed and connected to a data acquisition (DAQ) system. B-mode, color Doppler, and spectral Doppler data could all be collected with SS-19-128. The imaging resolution and penetration capacity of SS-19-128 were characterized on phantoms. Five human subjects were recruited to demonstrate B-mode and Doppler imaging by SS-19-128. Gingival thickness was measured on 11 swine teeth by SS-19-128 for comparison to conventional transgingival probing via Bland-Altman analysis and Pearson correlation. ResultsThe axial and lateral spatial resolution at 5.5 mm depth is 102.1 m and 142.9 m, respectively. The penetration depth in a tissue-mimicking phantom is over 30 mm. In vivo B-mode imaging of all 28 teeth was demonstrated on one human subject, and imaging of tooth #18 was accessed on five human subjects. Gingival thickness measurement compared with transgingival probing showed a bias of -0.015 mm and SD of 0.031 mm, and a r = 0.9235 (P<0.0001) correlation. In vivo color and spectral Doppler imaging of the supraperiosteal artery in human gingiva was performed to generate hemodynamic information. ConclusionsThe small size of SS-19-128 offers important advantages over existing technology--more specifically, whole-mouth scanning/charting reminiscent of radiography. This is nearly a two-fold increase in the number of teeth that can be assessed versus existing transducers.

bioengineering↗

bioRxiv2022

Full-mouth photoacoustic/ultrasound imaging of the periodontal pocket with a compact intraoral transducer

Periodontitis is a public issue and imaging periodontal pocket is important to evaluate periodontitis. Regular linear transducers have limitations in imaging the posterior teeth due to their geometry restrictions. Here we characterized a transducer that can image the entire human mouth including assessment of periodontal pockets via a combination of photoacoustic and ultrasound imaging. Unlike conventional transducer design, this device has a toothbrush-shaped form factor with a side-view transducer to image molars (total size: 1 x 1.9 cm). A laser diode was integrated as the light source to reduce the cost and size and facilitates clinical transition. The in vivo imaging of a molar of a periodontal patient demonstrated that the transducer could image in the posterior area of gum in vivo; the value determined by imaging was within 7% of the value measured clinically.

bioengineering↗